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Connatal bacterial pneumonia is common in neonates. Animal studies and initial clinical reports indicate that surfactant dysfunction is involved in the pathophysiology of severe neonatal pneumonia. Since respiratory distress syndrome and connatal pneumonia may be difficult to differentiate in the first hours of life, neonates with respiratory failure due to bacterial infections might receive surfactant. Under such conditions surfactant components might be catabolized by bacteria and promote bacterial growth. We therefore investigated the influence of three modified natural (Curosurf, Alveofact, and Survanta) and two synthetic (Exosurf and Pumactant) surfactant preparations on the growth of bacteria frequently cultured from blood or tracheal aspirate fluid in the first days of life. Group B streptococci (GBS), Staphyloccocus aureus, and Escherichia coli were incubated in a nutrient-free medium (normal saline) for 5 h at 37 degrees C, together with different surfactants at concentrations of 0, 1, 10, and 20 mg/ml. With the exception of E. coli, incubation in saline alone led to a variable decrease in CFU. In the presence of Alveofact, Exosurf, and Pumactant the decline in bacterial numbers was less marked than in saline alone. Curosurf was bactericidal in a dose-dependent fashion for GBS and had a strong negative impact on the growth of a GBS subtype that lacked the polysaccharide capsule. In contrast, Survanta (10 and 20 mg/ml) significantly promoted the growth of E. coli, indicating that surfactant components may actually serve as nutrients. We conclude that bacterial growth in different surfactant preparations is influenced by microbial species and the composition and dose of the surfactant. Further studies are necessary to elucidate the mechanisms behind our findings and to evaluate the effects of surfactant on bacterial growth in vivo.

In newborn infants, group B streptococci (GBS) often cause pneumonia, with polymorphonuclear leukocytes (PMN) migrating into the lungs. Because surfactant therapy may be needed in such patients, we evaluated the interaction between GBS or GBS-stimulated PMN and a surfactant preparation (Curosurf) in vitro. The superoxide production of GBS strains or GBS-activated PMN was measured, using the nitroblue tetrazolium (NBT) test and the subsequent lipid peroxidation (LPO) as the content of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE). The growth of GBS in surfactant was determined and related to the LPO. Finally, the effect of LPO on surfactant activity, caused by GBS-stimulated PMN, was assessed by measuring dynamic surface tension in a pulsating bubble surfactometer. Curosurf diminished the NBT reduction by both live GBS and GBS-stimulated PMN. Surfactant was peroxidized by reactive oxygen species (ROS) from both GBS and GBS-stimulated PMN in a time-dependent manner. Vitamin E significantly reduced the peroxidation level of surfactant in both cases. Surfactant peroxidation was associated with a reduction in the number of live bacteria. The biophysical activity of Curosurf was impaired by GBS-stimulated PMN, as reflected by increased minimum surface tension during cyclic compression. These findings indicate that Curosurf undergoes LPO by ROS produced by GBS and/or PMN. We speculate that exogenous surfactant preparations should be supplemented with vitamin E or another antioxidant, when given to infants with GBS pneumonia.

Oxygen toxicity and mechanical ventilation are main factors in the development of chronic lung disease in preterm infants. We examined two antioxidant enzymes, superoxide dismutase (SOD) and catalase, in tracheal fluid of preterm infants with severe respiratory distress syndrome (RDS) treated with surfactant. SOD and catalase catalyse the transformation of oxygen radicals and hydrogen peroxide to less toxic metabolites. 31 preterm infants were randomised to either single or multiple dose treatment with surfactant (Curosurf). Tracheal aspirates were obtained during routine tracheal suctioning and the two enzymes were measured during the first week of life. 11 of 31 preterm babies (35%) did not show any SOD-activity in tracheal fluid. Four out of the eleven preterm infants developed bronchopulmonary dysplasia. Patients receiving multiple dose treatment had significantly higher SOD-activity (> 10 micrograms/mg albumin, p < 0.01) than patients with single dose treatment. Only 2 of 31 preterm babies (6%) lacked catalase activity in tracheal aspirate. 94% had catalase activity between 1 and 12 micrograms/mg albumin. We conclude that, the majority of preterm infants with severe RDS do not have protective superoxide dismutase activity in tracheal fluid. Following multiple dose surfactant replacement significantly higher SOD activity was observed as compared to single dose therapy.

Neonates suffering from group B streptococcal (GBS) pneumonia often lack type-specific opsonizing antibodies. We studied the influence of combined intratracheal treatment with surfactant and a specific antibacterial polyclonal antibody (IgG fraction) on bacterial proliferation and lung function in an animal model of GBS pneumonia. Near-term newborn rabbits received an intratracheal injection of either the specific IgG antibody, nonspecific IgG, surfactant, a mixture of surfactant and the antibody, or 0.9% saline. At 30 min the rabbits were infected with a standard dose (10(8)) of the encapsulated GBS strain 090 Ia. After 5 h of mechanical ventilation the mean estimated increase in bacterial number in lung homogenate (log10 colonies/g) was 0.76 in the antibody group, 0.92 in the nonspecific IgG group, 0.55 in the surfactant group, and 1.29 in the saline group. A mean decrease in bacterial number (-0.05) was observed in the group that received combined treatment with surfactant and antibody (p < 0.05 versus all other groups). Lung-thorax compliance was significantly higher in both groups of surfactant-treated animals compared with saline or IgG treatment. We conclude that in experimental neonatal GBS pneumonia combined treatment with surfactant and a specific immunoglobulin against GBS reduced bacterial proliferation more effectively than either treatment alone.

Surfactant protein A (SP-A) increases the resistance of surfactant to inhibition by plasma and other proteins. In a previous study we found that a monoclonal anti-SP-A antibody (R 5) increased the sensitivity of surfactant to inhibition by fibrinogen in vivo and in vitro. SP-A has been shown to stimulate microbial phagocytosis and killing by alveolar macrophages. We hypothesized that using R 5 to inactivate SP-A in an animal model mimicking congenital group B streptococcal (GBS) pneumonia might result in increased bacterial proliferation and a deterioration in lung function. Newborn near term rabbits were delivered by Cesarean section, anesthetized, tracheotomized, and ventilated for 5 h in a plethysmograph system allowing measurement of dynamic lung-thorax compliance. Postnatally the animals received one intratracheal injection (5 ml/kg) of R 5, nonspecific IgG, or normal saline. At 30 min all animals received a standard dose of an encapsulated GBS strain by intratracheal injection. The number of bacteria (mean log10 CFU/g lung +/- S.D.; CFU = colony forming unit) was evaluated in lung homogenates. Histologic lung sections were judged by light microscopy. Bacterial proliferation was similar in rabbits treated with the monoclonal antibody (9.33 +/- 0.39; n = 14) and in control animals receiving saline (9.16 +/- 0.35; n = 14) or nonspecific IgG (9.26 +/- 0.31; n = 11). No significant differences were noted on the histologic analysis or in measurements of lung function. We conclude that intratracheal instillation of a monoclonal anti-SP-A antibody did not increase bacterial proliferation in GBS-infected newborn rabbits. These findings suggest that SP-A does not play an important role in protection against encapsulated GBS strains in the neonatal period.

Background: Respiratory distress syndrome (RDS) due to surfactant deficiency remains a cause of considerable mortality in the neonatal period., Methods: In a retrospective study we analysed the records of 1109 premature newborns with a birth weight below 1500 g that were treated on our unit. RDS was assumed if the infants needed mechanical ventilation with oxygen supplementation and the typical radiological signs were present on chest x-ray., Results: No changes in the incidence of RDS were found during the period of observation. Below 29 weeks gestational age 90% of infants suffered from RDS (55% severe RDS grade III or IV). The incidence was 75% (grade III or IV: 32%) for infants born at 29 and 30 weeks, 48% (grade III or IV: 15%) at 31 and 32 weeks and 33% (grade III or IV: 6%) for neonates born at 33 weeks of gestation. Using a logistic regression analysis model the following parameters were found to increase the risk for RDS significantly (p < 0.05): no prenatal steroid treatment, Cesarean section, male gender, APGAR at 5 min < 7, metabolic acidosis (base excess < or = -6 mval) and rectal temperature < 36 degrees C on admission. Following gestosis, insufficiency of the placenta and premature rupture of membranes a decrease in the incidence of RDS was observed., Conclusion: We conclude that although some risk factors for RDS will be difficult to exclude (e.g. maternal disease, gender) the incidence and severity of RDS can be reduced by measures like maternal antenatal steroid treatment. Perinatal asphyxia (low APGAR values and/or acidosis) and hypothermia should be avoided, as these conditions increase the relative risk for developing RDS.

Aims: To study the influence of surfactant on lung function and bacterial proliferation in immature newborn rabbits with experimental group B streptococcal (GBS) pneumonia., Methods: Preterm rabbit fetuses (gestational age 28 days) underwent tracheotomy and were mechanically ventilated in a warmed body plethysmograph that permitted measurement of lung-thorax compliance. Fifteen minutes after the onset of ventilation the animals received either GBS or saline intratracheally; at 30 minutes, a bolus of saline or 200 mg/kg of a porcine surfactant (Curosurf) was administered via the airway. Bacterial proliferation was evaluated in lung homogenate at the end of the experiments and the results expressed as mean log10 cfu/g lung (SD). Animals receiving only saline (n = 20) or saline and surfactant (n = 20) served as controls., Results: The average survival time was about three hours in all groups. Infected animals receiving surfactant (n = 22) had significantly less bacterial growth (9.09 (0.45) vs 9.76 (0.91)) and improved lung function (compliance: 0.61 (0.14) vs 0.34 (0.19) ml/kg. cm H2O) than infected rabbits receiving saline at 30 minutes (n = 22)., Conclusion: Surfactant improves lung function and mitigates bacterial growth in preterm rabbits infected with group B streptococci.

It has been suggested that surfactant protein-A (SP-A) protects surfactant activity from inhibitors such as fibrinogen. Substantial evidence indicates that inhibition of surfactant activity is often important in the pathogenesis of acute respiratory failure. Studies on surfactant function in the pulsating bubble surfactometer imply that SP-A helps to maintain low surface tension in the presence of inhibitors such as fibrinogen. We tested whether SP-A acts in this way in vivo. Rabbit pups, 29 d gestational age, were treated with a monoclonal antibody to rabbit SP-A (R5) followed by fibrinogen, or with control preparations (normal IgG and saline, respectively). Lung compliance was measured during ventilation throughout these experiments. Air-space volume and pulmonary edema were quantitated morphometrically. Animals receiving anti-SP-A antibody + fibrinogen showed substantial and significant impairment in lung compliance compared with control littermates receiving normal IgG and/or saline. Lungs from these animals showed decreased pulmonary air-space volume and increased alveolar edema. We conclude that SP-A protects pulmonary surfactant from inhibition by fibrinogen in vivo. This protective activity may be important in the pathogenesis of both adult and neonatal respiratory distress syndromes, and it may also be useful in devising therapies for these diseases.

We measured alveolar-to-vascular leakage of surfactant protein A (SP-A) in immature newborn rabbits delivered at a gestational age of 27 days. Experimental animals received, via a tracheal cannula, 2 ml/kg of a mixture of modified porcine surfactant (Curosurf, 80 mg/ml) and human recombinant SP-A (4 mg/ml). Littermate controls received the same volume of human SP-A in saline (4 mg/ml). After 30 min of artificial ventilation with a frequency of 40/min and an inspiration time of either 0.75 or 0.45 s, blood was sampled from the right ventricle and the lungs were lavaged. The content of human SP-A in serum and lung lavage fluid was determined with ELISA kits, and the alveolar-to-vascular leak expressed as the quotient of total SP-A in serum and lavage fluid. The leak in control animals amounted to about 2% of SP-A in lung wash and was several times higher in these animals than in those receiving surfactant. The leak was of the same order irrespective of whether the animals were ventilated with long or short inspiration time. We speculate that serum levels of SP-A may reflect the degree of lung injury in various forms of respiratory failure.

Aims: To compare treatment regimens of two widely used natural surfactant preparations Curosurf and Survanta in respiratory distress syndrome (RDS)., Methods: The effects of the two treatment regimens on gas exchange, ventilatory requirements, and 28 day outcome in infants with RDS were compared. Seventy five preterm infants (birth weight 700-1500 g) with RDS requiring artificial ventilation with an FIO2 of > or = 0.4, were randomly selected at 1-24 hours of age. One group received an initial dose of Curosurf (200 mg/kg); the other group Survanta (100 mg/kg). Patients who remained dependent on artificial ventilation with an FIO2 of > or = 0.3 received up to two additional doses of Curosurf (each of 100 mg/kg) after 12 and 24 hours or up to three additional doses of Survanta (each of 100 mg/kg) between six and 48 hours after the initial dose., Results: There was a rapid improvement in oxygenation and ventilatory requirements were reduced in both groups. However, infants treated with Curosurf had a higher arterial:alveolar oxygen tension ratio and required a lower peak inspiratory pressure and mean airway pressure at several time points within 24 hours of randomisation (p < 0.05-0.001). The incidences of pneumothorax in the Curosurf and Survanta groups were 6% and 12.5%, respectively; the corresponding figures for grades 3-4 intracerebral haemorrhage were 3% and 12.5%, respectively. Mortality was 3% in the Curosurf group and 12.5% in the Survanta group. However, these differences did not reach significance., Conclusion: The Curosurf treatment regimen resulted in a more rapid improvement in oxygenation than Survanta and reduced ventilatory requirements up to 24 hours after start of treatment. This was associated with a trend towards reduced incidence of serious pulmonary and non-pulmonary complications.

Pregnancies complicated by the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP) have been associated with both a poor maternal and a poor neonatal outcome in several publications. Because many studies were small and gave only scant information regarding the infants, we analyzed the clinical course of 89 neonates born to mothers with the HELLP syndrome. Ninety-eight percent of the neonates were born by cesarean section. Infants with a maternal HELLP syndrome were often small for gestational age (39%). The incidence of perinatal asphyxia was found to be 5.6%. Additionally, the affected very low birthweight (VLBW) infants had relatively high incidences of leukopenia (21%), neutropenia (33%), and thrombocytopenia (33%). Initially, 54% of the LBW infants were found to have normoblasts and 25% erythrocytosis. The incidence of these changes in blood cell count increased with decreasing birthweight. Nosocomial infections occurred more often in infants with a reduced neutrophil count. The overall mortality rate was 56 per 1000. Comparing the statistics of the VLBW infants with a maternal HELLP syndrome (n = 32) to all infants with a birthweight less than 1500 g (n = 521) during the investigational period, we found a similar mortality rate (9.3% and 8.4%, respectively). The pulmonary morbidity was also similar. The incidence of intracranial hemorrhage in VLBW infants with a maternal HELLP syndrome was lower (12.5% versus 18.2%) and of necrotizing enterocolitis was higher (6.2% versus 1.9%).

We studied bacterial proliferation in relation to surfactant treatment in a model of neonatal group B streptococcal (GBS) pneumonia. Surfactant (Curosurf) was isolated from pig lungs with a method preserving only polar lipids and hydrophobic proteins. Near-term rabbit fetuses were ventilated in a body plethysmograph system. At 15 min, a suspension of GBS strain 090 Ia LD (5 mL/kg, concentration approximately 10(9)/mL) was instilled intratracheally. At 30 min, surfactant (n = 12) or sterile saline (n = 13) was administered via the airways (2.5 mL/kg). A control group (n = 12) received the same volumes of saline. After 5 h the animals were killed, and samples for blood cultures and blood gases were taken from the heart. The left lung was aseptically removed, weighed, homogenized, serially diluted, and cultured on blood agar plates. The results were expressed as mean log10 colony forming units/g lung +/- SD. Compared with animals (n = 12) killed immediately after GBS instillation (8.13 +/- 0.54), there was a significant increase in bacterial numbers in both groups ventilated for 5 h, but values for surfactant-treated animals (8.96 +/- 0.38) were lower than those for animals receiving saline (9.46 +/- 0.50; p < 0.05). After 5 h, 96% of GBS-infected animals had positive blood cultures. Light microscopic examination of the right lung of GBS-infected animals revealed inflammatory changes that tended to be less prominent in surfactant-treated rabbits. We conclude that intratracheal inoculation of near-term rabbits with GBS resulted in a significant bacterial proliferation during 5 h of ventilation and that bacterial growth was mitigated by treatment with surfactant.

Unlabelled: Within a randomized European multicentre trial the time of onset, severity and progression of intracerebral haemorrhages (ICH) were investigated prospectively by serial cranial ultrasonography in 343 ventilated infants with severe respiratory distress syndrome (RDS) following instillation of single or multiple doses of a natural porcine surfactant (Curosurf). In 148/343 infants (43%) ICH was diagnosed (grade I or II: 22%, grade III or IV: 21%). In 26 cases (8%) ICH was present on the ultrasound scan prior to surfactant instillation at a median age of 6 h. Incidence and severity of ICH was similar after single- or multiple-dose surfactant treatment. Using a logistic regression model the following risk factors predictive of ICH were defined: low birth weight, allocation to certain hospitals, vaginal delivery, Apgar score < or = 6, rectal temperature on admission < or = 36 degrees C, primary anaemia, acidosis prior to treatment, RDS grade IV in pre-treatment chest films and poor response to surfactant treatment., Conclusion: Our study provides supportive evidence that multiple doses of Curosurf do not increase the risk for ICH as compared to single-dose administration.

Background: Doses between 20 and 200 mg/kg body weight (bw) of different surfactant preparations have been recommended in clinical trials for the treatment of neonatal RDS; an optimal dose regimen of surfactant replacement therapy has not yet been defined. Aim of the present pilot study was the evaluation of pulmonary gas exchange in infants with severe RDS following the application of either a high (200 mg/kg bw) or a low (100 mg/kg bw) dose of a natural porcine surfactant (Curosurf)., Methods: 15 neonates were randomized to a high dose regimen, 17 infants to a low dose of surfactant. Apart from a lower 1 minute Apgar in the 100 mg/kg bw group, birth weight, gestational age, sex, 5 minute-Apgar and disease severity (arterial to alveolar oxygenation ratio (a/A-ratio): 0.10 +/- 0.03 [high dose], 0.11 +/- 0.06 [low dose], mean +/- SD) were well matched in both groups., Results: Following surfactant instillation there was a rapid improvement in oxygenation in both groups. The a/A-ratio was slightly higher in the 200 mg/kg bw group during the first 12 hours following surfactant replacement, but statistically this was significantly higher only 4 hours after treatment (0.38 +/- 0.11 vs. 0.24 +/- 0.13, mean +/- SD, p < 0.05)., Conclusion: The dose of 100 mg/kg bw Curosurf resulted in a rapid improvement in oxygenation and ventilatory requirements; only during the first hours following surfactant replacement there was a slight further improvement with the higher dose of 200 mg/kg bw. The impact of different dose regimens on outcome parameters still has to be defined by a larger clinical trial.

Background: An increasing incidence of systemic candidiasis has been reported in low birth weight infants requiring intensive care. We have retrospectively analyzed mucocutaneous Candida-colonization and infection rate in 422 preterm infants with a birthweight < 1,500 g., Methods: All infants were treated at the NICU, University of Göttingen, from 1/1985-5/1991. 359 neonates (85%) were on mechanical ventilation, no prophylactic antimycotic regimen was applied. Mucocutaneous swabs and cultures from various anatomic sites were regularly obtained from all infants., Results: 37/422 preterm infants (8.8%) had mucocutaneous colonization with candida, none of our patients developed systemic candidiasis. In 7 mechanically ventilated patients (1.9%) Candida albicans or Candida tropicalis was repeatedly detected in the bronchial secretions; 1 patient who had invasive Candida-pneumonia was effectively treated with 5-Fluocytosin and Fluconazol. 4/352 (1.1%) central silastic catheters were colonized with Candida albicans; none of these patients required specific treatment., Conclusion: The low rate of mucocutaneous Candida-colonization and invasive infection found in our patients may be explained--at least in part--by epidemiological and obstetrical factor as well as by the procedures of the neonatal management.

Background and Methods: Central catheters are an important prerequisite for adequate parenteral nutrition in preterm infants. However, a variety of complications have been shown to be associated with central lines: septicemica, thrombotic complications, mechanical complications. In this retrospective analysis we summarize our recent experience with central silastic catheters., Results: Within a five-year-period (1986-1990). 497 silastic-catheters were inserted in 366 high risk neonates (mean birthweight 1360 g; 1060-1740 g, 25.-75. percentile) treated at the NICU, Department of Pediatrics, University of Göttingen. 451 catheters which were placed in a central position, were removed after an average duration of 11 days (mean; 8-18 days, 25.-75. percentile). During the observation period, 62.8 percent of the catheters were purposely removed. Making use of the Kaplan-Meier-curve, we calculated how long the catheter could stay without complications; 50% of all catheters could be expected to be in place for 25 days. The incidence of septicemia was 1.9%, bacterial contamination of the catheters was evident in 22% of all central lines. The most predominant microorganisms responsible for catheter-contamination were coagulase-negative staphylococci. In addition, catheters were removed because of signs of phlebitis or suspected thrombotic complications (11.1%), and mechanical complications (dislocation, occlusion; 11.7%). Due to malposition of the central catheter two preterm infants developed pericardial effusions. There was no correlation between the site where the catheter was inserted and these complications., Conclusion: Central silastic catheters wherever clinically indicated are a valuable adjunct in the parenteral nutrition on high risk neonates.

In an international multicenter trial infants with clinical and radiological signs of severe RDS (age 2-15 h, birthweight 700-2,000 g, mechanical ventilation, FiO2 greater than or equal to 0.6, no complicating disease) were randomized to receive either a single dose (n = 176) or up to three subsequent doses (n = 167) of a natural porcine surfactant (Curosurf). Using a logistic regression model, the effects of therapy, birthweight, sex, hospital and other clinical factors on survival and various outcome parameters were evaluated. Mortality (13 vs. 21%, p less than 0.05) and the incidence of pneumothorax (9 vs. 18%, p less than 0.01) were significantly lower in the multiple-dose group. Low birthweight, hospital allocation, low Apgar score and initial disease severity were associated with an increased mortality. Low birthweight, hypothermia (admission temperature less than 36 degrees C) and acidosis (pH less than 7.25) prior to surfactant treatment could be identified as risk factors for the development of intracranial hemorrhage.

There is now convincing evidence that the severity of neonatal respiratory distress syndrome can be reduced by surfactant replacement therapy; however, the optimal therapeutic regimen has not been defined. This randomized European multicenter trial was designed to determine whether the beneficial effects of a single large dose of Curosurf (200 mg/kg) in babies with severe respiratory distress syndrome (arterial to alveolar oxygen tension ratio approximately 0.10) could be enhanced by using multiple doses of surfactant. Preterm neonates (birth weight 700 to 2000 g) with severe respiratory distress syndrome requiring artificial ventilation with fraction of inspired oxygen greater than or equal to 0.6 were randomized into two groups at an age of 2 to 15 hours. Both groups received the usual dose of Curosurf (200 mg/kg) immediately after randomization. In neonates randomized to receive multiple-dose treatment, two additional doses of Curosurf (100 mg/kg each) were instilled into the airways (12 and 24 hours after the initial dose) provided that the patients still needed artificial ventilation with fraction of inspired oxygen greater than 0.21. In both groups (single dose: n = 176, multiple doses: n = 167) there was a rapid improvement in oxygenation as reflected by a threefold increase in arterial to alveolar oxygen tension ratio within 5 minutes after surfactant instillation (P less than .001), and peak inspiratory pressure and mean airway pressure could be reduced significantly during the first 6 hours after surfactant treatment. In addition, ventilatory requirement (peak inspiratory pressure, ventilatory efficiency index) was reduced in the multiple-dose group 2 to 4 days after randomization (P less than .05 to .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Keratinocytes of stratified epithelia, including the epidermis, express two distinct forms of transglutaminase, type I and type II. Type I transglutaminase activity is responsible for cell envelope formation in terminally differentiating cultured keratinocytes. Transglutaminase enzymatic activity has been associated with several proteins that are differentially expressed in vivo and in vitro. To elucidate the relationship between the epidermally expressed transglutaminases, cDNA for type I transglutaminase was cloned from a human high-calcium keratinocyte lambda gt11 library. cDNA fragments, generated by PCR primed with a mixture of oligonucleotides coding for five invariant amino acids in the active site, were used as a screening probe. Based on the sequence analysis of 1653 nt contained in the lambda 1-126a clone and on the pattern of expression of a complementary approximately 3-kb transcript, we report cloning of the epidermal type I transglutaminase gene. The expression of this gene is regulated by calcium ions and retinoic acid in cultured human keratinocytes. There are highly conserved regions near the active site cysteine residues that may be important for the enzyme's specialized functions.

19 preterm infants with severe respiratory distress syndrome (RDS) were treated with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). 9 patients had a birth weight of less than 1000 g (845 +/- 112 g, mean +/- SD and the mean gestational age was 27.2 +/- 2.1 weeks). The other 10 had a birth weight of greater than 1000 g (1521 +/- 218 g and a mean gestational age 31 +/- 2.8 weeks). Age at treatment was 3 h in infants less than 1000 g and 4 h in patients greater than 1000 g. Both groups of infants showed a rapid improvement in oxygenation and gas exchange within minutes after surfactant replacement. Exposition to greater than 60% and greater than 40% oxygen was identical in both groups. However, time in greater than 21% oxygen was significantly longer in infants less than 1000 g (median 30 days, 8.5 days in patients greater than 1000 g, p less than 0.01). The duration of mechanical ventilation was 33 days, in patients greater than 1000 g and 5 days; p less than 0.01. None of the infants developed a pneumothorax, but 6 out of 9 patients less than 1000 g developed mild bronchopulmonary dysplasia. 2 infants less than 1000 g died at day 5 and day 11 from cardio-circulatory arrest following ligation of a patent ductus arteriosus, and nosocomial septicaemia, respectively. Prolonged mechanical ventilation and exposure to oxygen in patients less than 1000 g cannot be attributed to surfactant deficiency alone.(ABSTRACT TRUNCATED AT 250 WORDS)

26 preterm infants with severe respiratory distress syndrome (RDS) have been treated at different ages with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). Criteria for treatment included clinical and radiological signs of severe RDS (grade III-IV), requirement of artificial ventilation and an FiO2 greater than or equal to 0.6. Nineteen neonates have been subjected to early treatment (2-15 h of age, mean birth weight SD: 1201 +/- 387 g) and 7 patients to late treatment (greater than 15 h to 48 h of age, birth weight SD 1624 +/- 649 g). Average FiO2 before treatment was 0.88 in early-treated patients and 0.8 in late-treated patients, age at treatment was 4.6 h and 36 h, respectively (median). Both early- and late-treated infants exhibited an improvement in oxygenation (more than twofold increase of the PaO2/FiO2 ratio) within 5 minutes after initiation of therapy. Average duration of intermittent pressure ventilation was 15 days in the early treatment group and 19 days in the late treatment group. Total exposition to greater than 21% oxygen was 21 days in early-treated and 48 days in late-treated infants. Pneumothorax occurred in none of the patients. All early treated infants survived without signs of severe bronchopulmonary dysplasia (BPD greater than 21% O2, greater than 90 days plus radiological changes). However, two out of seven late-treated infants developed severe BPD; one patient died as a consequence of cardiopulmonary deterioration. Two patients in the early treatment group died of nonpulmonary complications. We conclude that surfactant replacement therapy should probably be initiated as soon as possible after manifestation of severe RDS.

Following perinatal asphyxia and intracranial hemorrhage frequently progressive ventricular dilatation develops in preterm infants. Most common is communicating hydrocephalus due to obliterative arachnoiditis. Ventricular dilatation is reported to affect normal brain development and early therapy is recommended. Cerebrospinal fluid shunting is still accompanied by multiple complications, esp. in preterm infants with a birth-weight below 1,500 g. Seven preterm infants, born between the 27th and 34th gestational week with a birthweight of 910-1,940 g were medically treated for their progressive communicating hydrocephalus. The therapy consisted of intermittant lumbar punctures, medication of acetazolamide and furosemide as well as electrolyte and base replacement. Therapy was started at the 14th-31st postnatal day and lasted from 46 to 149 days. In all children the ventricular dilatation diminished. A steady state of cerebrospinal fluid production and absorption was regained in four children. Due to reoccurrence of ventricular dilatation shunting was performed in three others at the age of more than 3 months and with a weight of 3,620-5,170 g. Thus, medical therapy of hydrocephalus provides time for development of preterm infants, delay of shunting procedures and normalisation of cerebrospinal fluid dynamics.